Preeclampsia is a syndrome defined by hypertension and proteinuria developed after twenty (20) weeks of gestation that also may be associated with myriad other signs and symptoms, such as oedema, visual disturbances, elevated liver enzyme, hemolysis, low platelets, headaches, and epigastric pain [1]. One sub-form of the disease, denoted HELLP, standing for hemolysis, elevated enzyme liver and low platelets, can occur with or without hypertension, and the term preeclampsia include this sub-form throughout this document. This disease complicates 3-7% of all pregnancies and is a multisystem maternal disorder that is the most common cause of death for both children and mothers during pregnancy. While the clinical manifestations appear from week 20, the underlying mechanisms may begin as early as at the time of implantation. As the disease progresses the disease may develop into its severe type called eclampsia, caused by angiospasmus in the brain and brain oedema that may result in severe epileptic seizures, stroke and death.
The etiology for preeclampsia is unknown but it is believed that during placentation, the invasion by the placental cells, the trophoblasts, into the uterus wall layer of the spiral arteries appears to be incomplete [2-3] and the severity of hypertension may be related to the degree of trophoblastic invasion [4]. Vasoconstriction and elevated resistance to blood flow follows as a consequence. The etiology is also described as decreased placental perfusion (or placental insufficiency), in combination with oxidative stress that causes general endothelial cell damage within the placenta which may result in endothelial inflammation, affecting the maternal vascular system and the vascularization of the kidneys.
About one third of cases develop in the first pregnancies. Other risk factors include multifetal gestations, conceiving through in-vitro fertilization, particularly oocyte donation, preeclampsia and hypertension disorders in a previous pregnancy, family history of preeclampsia, chronic hypertension, pregestational diabetes, vascular and connective tissue disease, nephropathy, antiphospholipid antibody syndrome, systemic lupus erythematosus (SLE), obesity, age 35 years and older, teenagers and African-American race [5]. Preeclampsia is a leading cause of maternal mortality and morbidity accounting for about 12-18% of all pregnancy-related maternal deaths. It is also associated with a high perinatal mortality and morbidity. The only curative treatment for preeclampsia today is to deliver the fetus and removal of the placenta.
Mothers who develop preeclampsia at pregnancy are at increased risk for cardiovascular diseases and diabetes, and their offsprings are at risk for obesity and diabetes, in addition to developmental disorders such as motor and cognitive disorders and blindness.
Reduced uterine perfusion associated with increased vascular resistance can be detected with Doppler ultrasound of the maternal uterine arteries. The increased impedance to the uterine artery perfusion, or increased pulsatility index and Doppler notch indicates that the mother may have a higher risk of developing preeclampsia, resulting in various endothelial problems such as a general endothelial inflammation. The symptoms of preeclampsia typically appear in the third trimester of pregnancy and are usually detected by routine monitoring of the woman's blood pressure and urine proteins
Currently, there are no known cures for preeclampsia except for delivery of the fetus. However, the decision to deliver a patient with preeclampsia must balance both maternal and fetal risks. Preeclampsia can vary in severity from mild to life threatening. A mild form of preeclampsia can remain mild with bed rest and frequent monitoring. For moderate to severe cases, hospitalization is necessary and blood pressure medication and anticonvulsant medications to prevent seizures are prescribed. If the condition becomes life-threatening to the mother or the baby, the only cure is to terminate the pregnancy often resulting in a prematurity of the newborn due to the pre-term delivery. There are two main goals of management of women with preeclampsia: prevention of seizures or eclampsia and control of hypertension. Magnesium sulfate has been used for the prevention of seizures, usually as an intravenous delivery. Daily calcium supplementation and early use of Aspirin may reduce the frequency of the disorder particularly if administered before 16 weeks. Antioxidant vitamins have not been shown to prevent preeclampsia. The management of blood pressure levels with the drugs labetalol or hydralazine has shown benefits although to a limited time.
Novel biomarkers have been found that may be used to detect the syndrome. One such is expressed in the placenta already during the first trimester and may be used to predict pregnancies at risk, a protein called placental protein 13 (PP-13) [6]. The concentration of PP-13 has been shown to be altered in maternal blood in pregnancy disorders such as preeclampsia. More recent studies have shown that the serum levels of PP-13 are significantly reduced at 6-13 weeks in cases developing early, as well as late-onset preeclampsia [7]. PP13 is a member of the β-galactoside binding S-type galectin superfamily and is only expressed in placental tissues of higher primates, and within the villous trophoblast it can only be found in the multinucleated syncytiotrophoblast [8]. PP-13 is expressed and released into the intervillous space, where it enters the maternal circulation and can be detected in maternal blood. While in unaffected pregnancies serum concentrations of PP-13 rise moderately from the first to the third trimester of pregnancy, women who develop preeclampsia start with a lower than normal PP-13 level in the first trimester, and a diagnostic test was develop to use the lower PP-13 level as a measure to predict high risk for preeclampsia. PP-13 levels sharply increase between the first to the third trimester in women who enter the active phase of the disease. This stip change in the level of PP-13 is further assisting in predicting the risk to develop the disorder